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Drug may be near for cancer's companion condition cachexia

Cachexia is the muscle wasting and weight loss that often accompany cancer's effects. Two potential treatments that may boost muscle strength are in Phase 3 clinical trials.

February 27, 2012|By Amber Dance, Special to the Los Angeles Times
  • Bonnie Addario didn't know there was a word for what was happening to her: cachexia. As if lung cancer weren't bad enough, the 54-year-old had lost 30 pounds off her normally 130-pound frame.
Bonnie Addario didn't know there was a word for what was happening… (James Hall )

Bonnie Addario didn't even know there was a word for what was happening to her. As if lung cancer weren't bad enough, the 54-year-old had lost 30 pounds off her normally 130-pound frame. Her life was limited to her husband's Barcalounger, where she had to recline because she lacked the strength to sit up straight.

"It affected everything I did," says Addario, who is alive and well nine years later in San Carlos, Calif. "I literally could not get up and down the stairs."

There is a name for what Addario experienced: cachexia. It is the muscle wasting and weight loss that are so often cancer's sidekick.

Doctors and patients have long assumed cachexia is an integral part of cancer, and it's rarely discussed. "Ninety percent of oncologists completely ignore the cachexia because there's no known therapy," says Alfred Goldberg, a professor of cell biology who studies protein and muscle breakdown at Harvard Medical School in Boston.

But that could soon change as two potential cachexia treatments are now in Phase 3 clinical trials. If studies continue to go well, the drugs could become available for lung cancer patients within the next two to three years.

The main goal of both medications is to give people more muscle strength as they fight cancer. But they may do even more, scientists hope.

"It's not clear that if you treat cachexia you will prolong life," says Dr. Egidio Del Fabbro, a palliative care physician at the University of Texas M.D. Anderson Cancer Center in Houston, but "we suspect it will." Del Fabbro is not involved with either of the companies developing the drugs,GTx Inc. of Memphis, Tenn., and Helsinn Therapeutics Inc. of Bridgewater, N.J.

Cachexia (pronounced kuh-KEK-see-uh) is commonly defined as the unintentional loss of 5% or more of a person's weight within a six-month period. Crucially, it's muscle that slides off one's frame, often with fat as well. It's associated with advanced cancers as well as HIV, heart failure and kidney disease. In layman's terms, it means "the patient looks awful, they look weak, they've lost much of their body mass," Goldberg says.

Cachexia is especially prevalent in pancreatic and lung cancers. People with the condition also tend to lose their appetites, but eating more does not help because the body's metabolism is operating at a higher-than-normal rate, says Vickie Baracos, a metabolism researcher at the University of Alberta in Edmonton.

"The controls are not operating properly," she says. "It's sort of like having your thermostat turned up and the window left open at the same time."

Given current rates of obesity, muscle wasting is sometimes hidden behind a layer of fat. "You can have somebody who technically looks obese, but they have the muscle mass of a concentration camp victim," says Dr. Mitchell Steiner, a urologic oncologist who co-founded GTx and now serves as the company's chief executive.

In the past, researchers have focused on destroying cancer. But now that many people survive, or live longer with cancer, some scientists are shifting their focus to medicines that improve the quality of life for patients, says Melinda Sheffield-Moore, a muscle physiologist at the University of Texas Medical Branch at Galveston.

Cachexia has a huge, and detrimental, effect on quality of life.

Dr. Richard Gralla, a medical oncologist at Hofstra University in New York City, has conducted two surveys of about 4,000 cancer patients and their caregivers; 83% of the patients reported that nutrition, loss of appetite and weight, and fatigue were "very important" or "important" concerns.

"This was among the very top issues for patients," says Gralla, who presented his survey results at the annual meetings of the American Society of Clinical Oncology in June and the San Antonio Breast Cancer Symposium in December. (He has also consulted for GTx.)

The weight loss is more than an inconvenient side effect. "Cancer kills, but cachexia can also kill if you lose a significant amount of muscle," Sheffield-Moore says. Weakened heart muscles might give out, the muscles needed to breathe may not perform adequately or general weakness can make a person susceptible to infections, she says.

In addition, wasting and weakness make it harder for a person to withstand the toxic effects of chemotherapy and radiation, so it may cut short treatment. Cachexia is a bad sign for recovery as well. "It sort of tells us that the cancer's winning," Sheffield-Moore says.

Scientists are just starting to understand the biology of cachexia. Part of the problem appears to be that cancer and its treatments create inflammation — normally a healthy response to disease — but for some reason it goes haywire and triggers the muscle breakdown.

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